Seizure threshold to lidocaine is decreased following repeated ECS (electroconvulsive shock)

Abstract

Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS all rats received a lidocaine challenge (LC) in the form of an intraperitoneal (IP) injection of lidocaine (65 mg/kg). After the injection the animals were observed for occurrence of motor seizures. A total of 67% (10/15), 47% (7/15), and 0% (0/18) of the daily, weekly, and sham groups, respectively, had motor seizures in response to the LC. In the second experiment five groups of rats received an ECS daily for 0, 1, 6, 18, and 36 days, respectively. Eighteen weeks after the last ECS all rats received an LC and 0% (0/15), 13% (2/15), 20% (3/15), 53% (8/15), and 58% (7/12), respectively, developed seizures in response to the LC. In the third experiment two groups of rats received daily ECS and sham-ECS, respectively. Twenty-four hours after the last ECS all rats received an LC. A total of 60% (9/15) of the ECS group and 0% (0/10) of the sham-ECS group had seizures in response to the LC. The study demonstrates a decrease in seizure threshold to lidocaine in ECS-pretreated rats as early as 1 day and as late as 18 weeks following the last ECS, and a positive correlation between the number of ECS administered and the proportion of animals having seizures in response to the LC was found. The convulsant effect of lidocaine has been proposed to be mediated through binding on the GABA receptor-ionophore complex. Therefore this study suggests that ECS causes long-lasting, possibly permanent, changes within the GABA-ergic system.